Induction and dorsal restriction of Paired-box 3 (Pax3) gene expression in the caudal neuroectoderm is mediated by integration of multiple pathways on a short neural crest enhancer.

Pax3 encodes a paired-box transcription factor with key roles in neural crest and neural tube ontogenesis. Robust control of Pax3 neural expression is ensured by two redundant sets of cis-regulatory modules (CRMs) that integrate anterior-posterior (such as Wnt-ßCatenin signaling) as well as dorsal-ventral (such as Shh-Gli signaling) instructive cues. In previous work, we sought to characterize the Wnt-mediated regulation of Pax3 expression and identified the Cdx transcription factors (Cdx1/2/4) as critical intermediates in this process. We identified the neural crest enhancer-2 (NCE2) from the 5'-flanking region of Pax3 as a Cdx-dependent CRM that recapitulates the restricted expression of Pax3 in the mouse caudal neuroectoderm. While this is consistent with a key role in relaying the inductive signal from posteriorizing Wnt ligands, the broad expression of Cdx proteins in the tailbud region is not consistent with the restricted activity of NCE2. This implies that other positive and/or negative inputs are required and, here, we report a novel role for the transcription factor Zic2 in this regulation. Our data strongly suggests that Zic2 is involved in the induction (as a direct Pax3NCE2 activator and Cdx neural cofactor) as well as the maintenance of Pax3 dorsal restriction (as a target of the ventral Shh repressive input). We also provide evidence that the inductive Cdx-Zic2 interaction is integrated on NCE2 with a positive input from the neural-specific transcription factor Sox2. Altogether, our data provide important mechanistic insights into the coordinated integration of different signaling pathways on a short Pax3 CRM.

Children and adolescents' mental health in pandemics and confinement: A scoping review of vulnerability factors and repercussions.

Children and adolescents are a population at particular risk of experiencing adverse mental health repercussions related to pandemics. To understand vulnerability factors and repercussions of pandemics and related sanitary measures on children and adolescents' mental health, we performed a scoping review to examine and synthesize literature. In total, 66 articles were included. Results present: (1) factors that increase vulnerability to adverse mental health repercussions (e.g., having a pre-existing mental health condition, social isolation, low socio-economic status, parental distress, and overexposure to media content) and (2) specific mental health repercussions (e.g., anxiety, fear, depression, and externalizing behaviors). Addressing concerns underlined in this review could contribute to preventing further negative mental health repercussions of pandemics for children and adolescents and better prepare governments and professionals to address these highly challenging situations. Recommendations for practice include enhancing healthcare professionals' awareness about possible detrimental repercussions pandemics and sanitary measures have on children and adolescents' mental health, assessing changes for those with pre-existing mental health conditions, allocating funding for telehealth research, and providing greater support to healthcare providers.

Children and adolescents' mental health during the COVID-19 pandemic: A qualitative study of their experiences.

TOPIC: Public health measures implemented in response to the COVID-19 pandemic severely disrupted children and adolescents' (C&A) lives, affecting their sense of structure, predictability, and security. PURPOSE: To examine C&A' experiences during the COVID-19 pandemic to better understand how this context and its associated public health measures affected them and their mental health, and to identify helpful coping strategies. SOURCES USED: The study was guided by a participatory hermeneutic framework. Semistructured interviews were conducted with 25 C&A aged 6-17 years during the first and second pandemic waves. Participants' interviews were analyzed following a narrative synthesis approach, through which C&A' experiences were contrasted and contextualized to highlight relevant themes. CONCLUSIONS: Participants described a distinct pattern related to their mental health as the pandemic unfolded, which followed the severity of the pandemic in the province. Negative repercussions on their mental health were linked to the loss of social activities, imposed public health measures, transition to online learning, and challenges with family relationships. Certain youth shared positive societal and moral reflections triggered by the pandemic context. Coping strategies reported include: having a variety of hobbies; expressing their emotions; and accessing financial and material resources. This study highlights the importance of supporting C&A' mental health during crisis situations such as a pandemic. Their perspectives are vital for clinical practice and policy improvement, particularly to find means for social engagement while maintaining safety.